Comparative Transcriptomic and Epigenomic Analysis Highlights Hepatitis B Virus Infection Impact on Hepatocellular Carcinoma Development

Abstract

Hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC), yet the molecular events linking infection to malignant transformation remain incompletely defined. Here, we integrated transcriptomic (RNA-seq) and epigenomic (ChIP-seq for H3K27ac and H3K27me3) data across normal hepatocyte-derived cells (WT), HBV-infected cells, and HCC samples to quantify gene expression changes and epigenetic remodeling during disease progression. Transcriptomic profiling revealed distinct sets of differentially expressed genes (DEGs) between WT, HBV, and HCC states, with enrichment in pathways related to chromatin organization, signal transduction, lipid metabolism, and immune regulation. Epigenomic analyses demonstrated that HBV infection contributes to widespread redistribution of histone modifications, with reduced H3K27me3 at promoter regions and increased H3K27ac at enhancer regions, favoring activation of oncogenic programs. Differential histone regions (DHRs) overlapped with DEGs involved in ribosomal activity, ubiquitin-like protein function, and chromatin dynamics, suggesting coordinated transcriptomic and epigenomic reprogramming. Together, these results suggest that HBV infection establishes an epigenetic landscape that persists into HCC and drives altered gene expression in pathways central to lipid metabolism, chromatin structure, and cell cycle progression. This work highlights candidate biomarkers and regulatory mechanisms underlying HBV-associated hepatocarcinogenesis.